From molecules to populations energy budgets in the causality of toxic effects

1. From molecules to populationsenergy budgets in the causality of toxic effects Tjalling Jager Dept. Theoretical Biology

2. Dept. Theoretical Biology Aim: ‘Quantitative bioenergetics’

3. Dept. Theoretical Biology Aim: ‘Quantitative bioenergetics’ • Head of dept.: Prof. Bas Kooijman • Permanent staff: Dr. Bob Kooi and Dr. Tjalling Jager • PhD students in Amsterdam: • Jan Baas : NoMiracle, mixture toxicity • Daniel Bontje : ModelKey, food-chain toxicity • Anne Willem Omta : organic carbon pump • Jorn Bruggeman : organic carbon pump • George van Voorn : bifurcation analysis

4. effects on individual/population toxicant Causality How to link toxicant concentrations to whole-organism and population effects? NOEC/ECx CBR MoA energy budgets

5. Precondition 1 All concepts in causality chain should explicitly consider exposure time • Toxicity is a process in time • uptake into organism takes time • biomarker responses can/will change in time • NOEC/ECx/CBR values can/will change in time

6. carbendazim pentachlorobenzene time time EC10 in time Alda Álvarez et al. (2006) body length survival concentration body length cumul. repro cumul. repro

7. Precondition 2 Causality chain should cover all life-history aspects • Feeding, development, growth and reproduction are linked … • NOEC/ECx/CBR differ between endpoints • what about molecular mechanism of action?

8. A. nanus C. elegans body size body size EC10 reproduction reproduction time time ‘Narcotic’ effects

9. effects on individual/population Causality of effects toxicant statistics e.g., NOEC/ECx

10. toxicant target site effects on individual/population molecular mechanism Causality of effects CBRs etc.

11. toxicant target site effects on individual/population molecular mechanism physiological mechanism Causality of effects rest of the organism ENERGY BUDGET

12. Energy budgets

13. assimilation reproduction maintenance growth Energy budgets Each ‘MoA’ has specific effects on life cycle (direct/indirect)

14. DEB theory assimilation reproduction Kooijman (2000) (first edition 1993) maintenance growth

15. DEB theory Quantitative theory; ‘first principles’ • time, energy and mass balance Life-cycle of the individual • links levels of organisation: molecule  ecosystems Fundamental, but practical applications • bioproduction, biodegradation, (eco)toxicity, sewage treatment, climate change, … Kooijman (2000) (first edition 1993)

16. food faeces assimilation reserves somatic maintenance maturity maintenance  1- maturity offspring structure DEB allocation rules

17. Toxicants: DEBtox toxicokinetics energy-budget parameter DEB model Life-cycle effects Kooijman & Bedaux, 1996 (Wat. Res.) Jager et al., 2006 (Ecotoxicology)

18. triphenyltin body length cumulative offspring time time Target: maintenance Crommentuijn et al. (1997), Jager et al. (2004)

19. pentachlorobenzene body length cumulative offspring time time Target: costs for growth Alda Álvarez et al. (2006)

20. Chlorpyrifos body length cumulative offspring time time Target: hazard to embryo Crommentuijn et al. (1997), Jager et al. (2007)

21. food faeces assimilation reserves somatic maintenance maturity maintenance k k 1 - maturity structure offspring ‘Non-toxicant’ effects • ‘Gigantism’ • parasites in snails and Daphnia • Decreased size at maturity • parasites and kairomones in Daphnia Gorbushin and Levakin (1999)

22. Experiments nematodes Species • Caenorhabditis elegans and Acrobeloides nanus Chemicals • cadmium, pentachlorobenzene and carbendazim Exposure • in agar Endpoints • survival, body size, reproduction over full life cycle Alda Álvarez et al., 2005 (Func. Ecol.), 2006 (ES&T), 2006 (ET&C)

23. C. elegans and cadmium length eggs Mode of action: assimilation length survival Alda Álvarez et al. (2005) time (days)

24. A. nanus and cadmium Mode of action: costs for growth Alda Álvarez et al. (2006)

25. Physiological MoA

26. Physiological MoA

27. Physiological MoA

28. Physiological MoA

29. assimilation reproduction maintenance growth Population consequences

30. Population consequences

31. Population consequences

32. assimilation reproduction maintenance growth Population consequences Each ‘MoA’ has specific effects for populations

33. Extrapolate to populations Constant environment: populations grow exponentially • ‘intrinsic rate of increase’ • calculate from reproduction and survival in time

34. 1 0.4 0.4 0.4 0.8 0.3 0.3 0.3 0.6 intrinsic rate (d-1) 95% 0.2 0.2 0.2 0.4 90% 0.2 0.1 0.1 0.1 90% 95% 0 0 0 0 0 0 0 2 2 4 4 6 6 8 8 10 10 12 12 0 2 4 6 8 10 12 concentration (mg/L) concentration (mg/L) Extrapolate to populations Mode of action: costs for growth Mode of action: assimilation Cadmium

35. Conclusions Simple summary statistics are quite useless … • NOEC/ECx change in time and differ between endpoints • not helpful to derive CBRs on basis of ECx Molecular mechanism is important, but … • not enough to explain effects on life cycle/population Energy budgets must be considered • direct link to life-history and population effects • cover direct and indirect effects

36. toxicant target site phys. process maintenance effect on life cycle/population reproduction … Outlook Collaboration with CEH Monks Wood • life-cycle experiments with C. elegans • DEBtox analysis and micro-array work ?

37. toxicant target site phys. process maintenance effect on life cycle/population reproduction … Outlook Why useful? • number of chemicals and species is very large … • but number of target sites and processes is limited! ? www.bio.vu.nl/thb